The objective of this proposal is to determine whether prostaglandin (PG) E2 regulates immunoglobulin production within inflamed gingival tissue. Several components of bacterial plaque which accumulate during the onset of periodontal disease have been reported to polyclonally activate B lymphocytes leading to local immunoglobulin production. It has been shown that B cells extracted from gingival tissue display surface proteins associated with an activated B lymphocyte phenotype and spontaneously secrete antibody, mainly of the IgG class. Thus, experimental evidence strongly suggests that B cells within the inflamed gingival milieu are activated and that local class switching to IgG is an ongoing event. It has led to the hypothesis that polyclonal B cell activation may help to eliminate plaque but paradoxically potentiate periodontal pathology by exacerbating a local inflammatory response. The goal of this project is to evaluate whether PGE2 promotes the production of particular subclasses of IgG within inflamed gingival tissue. Increased levels of crevicular fluid PGE2 have been shown to be a positive indicator for ongoing loss of clinical periodontal attachment at specific sites around teeth. In addition, PGE2 has been shown to induce alveolar bone resorption. PGE2 may also function as a mediator of tissue destruction via an immunoregulatory mechanism. Studies in the murine model have demonstrated that PGE2 can potentiate cytokine-induced class switching in B cells following antigen-specific or polyclonal challenge. Therefore, we will investigate whether PGE2 can augment the production of particular IgG subclasses in mononuclear cells extracted from gingival tissue, as well as in purified, long term, factor-dependent gingival B cell lines. This is important since specific subclasses of IgG, such as IgGI and IgG3, can initiate the complement cascade and can activate Fc- gamma-R positive cells, including macrophages and neutrophils, following ligand binding. Activation of neutrophils and macrophages induces the release of proteolytic enzymes and reactive oxygen metabolites which cause an intense inflammatory reaction and local tissue damage. These studies will help to determine if elevated levels of PGE2 within inflamed gingival tissue enhance local immunoglobulin production and augment the synthesis of specific IgG subclasses.